Field
The application relates to nanostructured dispersions that can be used to effectively treat disorders and diseases of the eye by administering the dispersions on the ocular surface, in the anterior chamber, and in the posterior chamber.
Background Information
Many ophthalmic formulations include drug crystals suspended in ointments which are composed of mineral oil and petrolatum. Such formulations often result in irritation of the eye and patient non-compliance due to blurry vision and inconvenience. Other ophthalmic formulations are eye-drops containing drug suspensions in an aqueous solution, some of them viscous to extend residence time on the ocular surface.
The effective use of eye-drops is limited by the fact that many therapeutically valuable agents cause local irritation when topically dosed to the eye. The cornea is highly sensitive to the application of chemical agents. As such, this sensitivity significantly limits the use of many otherwise valuable therapeutic agents.
Another issue with existing ocular drug formulations is poor bioavailability of the drug. For example, poorly soluble drugs delivered to the front of the eye as a suspension, e.g., eye drops, must dissolve prior to being absorbed into the eye by diffusion. Problematically, the rate of drug dissolution is typically much slower than the rate of fluid clearance from the ocular surface. Thus, ineffective drug absorption, i.e., poor bioavailability, is one of the issues that confounds front-of-the-eye drug delivery.
To address this issue, insoluble or poorly soluble drugs, e.g., prostaglandins and difluprednate, are typically dissolved in an organic excipient followed by emulsification in an aqueous vehicle. The use of emulsions frequently leads to irritation of the ocular surface, resulting from the use of excipients that cause ocular surface inflammation. This is especially true when the medication is utilized for chronic ocular surface disease therapies, such as therapies for glaucoma, dry eye, and allergies.
Further, emulsions are inherently unstable, resulting in coalescence and subsequent separation of the phases.
The issues are different for back-of-the-eye diseases. For example, drug suspensions of triamcinolone acetonide have been injected intravitreally to alleviate inflammation resulting from diabetic macular edema. Multiple injections into the posterior segments of the eye can cause endophthalmitis and gradual retinal detachment.
The need exists for formulations for ocular administration which are non-irritating, stable, and capable of delivering a drug at therapeutic concentrations for an extended period. Additionally, a sustained release delivery system that is non-toxic and membrane-mimetic is needed for the treatment of back-of-the-eye diseases.